Dietary fibers (DFs) and their metabolites attract significant attention in research on health and disease, attributing to their effects on regulating metabolism, proliferation, inflammation, and immunity. When fermented by gut microbiota, DFs mainly produce short-chain fatty acids (SCFAs), such as acetic acid, propionic acid, and butyric acid. As the essential nutrients for intestinal epithelial cells, SCFAs maintain intestinal homeostasis and play essential roles in a wide range of biological functions. SCFAs have been found to inhibit histone deacetylase, activate G protein-coupled receptors, and modulate the immune response, which impacts cancer and anti-cancer treatment. Notably, while extensive studies have illuminated the roles of SCFAs in colorectal cancer development, progression, and treatment outcomes, limited evidence is available for other types of cancers. This restricts our understanding of the complex mechanisms and clinical applications of SCFAs in tumors outside the intestinal tract. In this study, we provide a comprehensive summary of the latest evidence on the roles and mechanisms of SCFAs, with a focus on butyric acid and propionic acid, derived from microbial fermentation of DFs in cancer. Additionally, we recapitulate the clinical applications of SCFAs in cancer treatments and offer our perspectives on the challenges, limitations, and prospects of utilizing SCFAs in cancer research and therapy.

Amyotrophic lateral sclerosis (ALS), characterized by a loss of motor neurons in the brain and spinal cord, is a relatively rare but currently incurable neurodegenerative disease. The global incidence of ALS is estimated as 1.75 per 100,000 person‐years and the global prevalence is estimated as 4.1–8.4 per 100,000 individuals. Contributions from outside the central nervous system to the etiology of ALS have been increasingly recognized. Gut microbiome is one of the most quickly growing fields of research for ALS. In this article, we performed a comprehensive review of the results from existing animal and human studies, to provide an up‐to‐date summary of the current research on gut microbiome and ALS. In brief, we found relatively consistent results from animal studies, suggesting an altered gut microbiome composition in experimental ALS. Publication bias might however be a concern. Findings from human studies are largely inconclusive. A few animal and human studies demonstrated the usefulness of intervention with microbial‐derived metabolites in modulating the disease progression of ALS. We discussed potential methodological concerns in these studies, including study design, statistical power, handling process of biospecimens and sequencing data, as well as statistical methods and interpretation of results. Finally, we made a few proposals for continued microbiome research in ALS, with the aim to provide valid, reproducible, and translatable findings.

Epigenetic downregulation of the ISG15–conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma Epigenetic downregulation of the ISG15–conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma

Serological detection of Epstein-Barr virus (EBV) antibodies is frequently used in nasopharyngeal carcinoma (NPC) mass screening. However, the large number of seropositive subjects who require close follow-up is still a big burden. The present study aimed to detect the nasopharyngeal EBV load in a high-risk population seropositive for antibodies against EBV, as well as to examine whether assay for nasopharyngeal EBV DNA load might reduce the number of high-risk subjects for follow-up and improve early detection of NPC. A prospective and population-based cohort study was conducted in southern China from 2006 through 2013. Among 22,186 participants, 1045 subjects with serum immunoglobulin A (IgA) antibodies against viral capsid antigen (VCA) titers ≥ 1:5 were defined as high-risk group, and were then followed-up for NPC occurrence. Qualified nasopharyngeal swab specimens were available from 905 participants and used for quantitative PCR assay. Our study revealed that 89% (802/905) subjects showed positive EBV DNA in nasopharyngeal swab. The nasopharyngeal EBV load in females was higher than that in males. The nasopharyngeal EBV load increased with increasing serum VCA/IgA titers. Eight cases of newly diagnosed NPC showed an extremely elevated EBV load, and 87.5% (7 of 8 patients) were early-stage NPCs. The EBV loads of 8 NPCs were significantly higher than those of 897 NPC-free subjects (mean, 2.8×10⁶ copies/swab [range 4.8×10⁴-1.1×10⁸] vs. 5.6×10³ [range 0-3.8×10⁶]). Using mean EBV load in NPC-free population plus two standard deviations as cut-off value, a higher diagnostic performance was obtained for EBV load test than serum VCA/IgA test (area under ROC, 0.980 vs 0.895). In conclusion, in a prospective and population-based study we demonstrated that an additional assay of EBV load in the nasopharynx among high-risk individuals may reduce the number of subjects needed to be closely followed up and could serve as part of a NPC screening program in high-risk populations.

Oral health and changes in the oral microbiome have been associated with both local and systemic cancer. Poor oral hygiene is a known risk factor for nasopharyngeal carcinoma (NPC), a virally associated head and neck cancer endemic to southern China. We explored the relationship between NPC and the oral microbiome using 16S rRNA sequencing in a study of 499 NPC patients and 495 population-based age and sex frequency-matched controls from an area of endemicity of Southern China. We found a significant reduction in community richness in cases compared to that in controls. Differences in the overall microbial community structure between cases and controls could not be explained by other potential confounders; disease status explained 5 times more variation in the unweighted UniFrac distance than the next most explanatory variable. In feature-based analyses, we identified a pair of coexcluding Granulicatella adiacens amplicon sequence variants (ASVs) which were strongly associated with NPC status and differed by a single nucleotide. The G. adiacens variant an individual carried was also associated with the overall microbial community based on beta diversity. Co-occurrence analysis suggested the two G. adiacens ASVs sit at the center of two coexcluding clusters of closely related organisms. Our results suggest there are differences in the oral microbiomes between NPC patients and healthy controls, and these may be associated with both a loss of microbial diversity and niche specialization among closely related commensals. IMPORTANCE The relationship between oral health and the risk of nasopharyngeal carcinoma (NPC) was previously established. However, the role of oral microbiome has not been evaluated in the disease in a large epidemiological study. This paper clearly establishes a difference in the oral microbiomes between NPC patients and healthy controls which cannot be explained by other confounding factors. It furthermore identifies a pair of closely related coexcluding organisms associated with the disease, highlighting the importance of modern methods for single-nucleotide resolution in 16S rRNA sequence characterization. To the best of our knowledge, this is one of the first examples of cancer-associated niche specialization of the oral microbiome.